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homogeneous anti-HER2 ADC 6 is an experimental antibody-drug conjugate (ADC) specifically engineered to treat glioblastoma multiforme (GBM) by overcoming the blood-brain barrier (BBB). It consists of the anti-HER2 monoclonal antibody trastuzumab site-specifically conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable valine-citrulline (vc) linker. Unlike conventional ADCs which are often heterogeneous mixtures with varying drug-to-antibody ratios (DAR), ADC 6 is a homogeneous construct with a precise DAR of 2. Research indicates that this high level of homogeneity and optimized payload loading are critical for effective BBB penetration, as overly drug-loaded species in heterogeneous mixtures tend to exhibit poor brain tumor targeting. In preclinical orthotopic models, ADC 6 demonstrated superior antitumor effects and survival benefits compared to its heterogeneous counterparts.
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